The mechanism of the bronchial hypersensitivity to histamine and methacholine remains the focal point of our investigation and is one factor common to both allergic and non-allergic patients with bronchial asthma. Although an imbalance in the autonomic nervous system has been suspected as a cause of the hypersensitivity in bronchial asthma for several decades, our studies in animals provides supportive evidence for such a theory. The nature of the defect resulting in bronchial hypersensitivity can also be studied in vitro. Thus, a more direct approach will be the use of radioligand binding techniques to determine the presence and quantity of alpha and beta adrenergic receptors in lung tissue from individuals with and without airway disease. The objective of these studies is to determine if a relationship exists between the number of functionally intact adrenergic receptors and the pharmacological responses of airways in appropriate animal models, as well as human airway smooth muscle. The effect of various substances known to increase or decrease these responses will be studied by comparing animals treated with agents that may alter the sensitivity of alpha receptors and/or beta receptors such as steroid and thyroid hormones, pertussis vaccine and endotoxin and denervation supersensitivity induced with 6-OH dopamine. Bronchial tissue will be studied for a functional deficiency of beta adrenergic receptors or a hypersensitivity of alpha adrenergic receptors. The possible role of endotoxin and infection or adrenergic receptors in asthma and chronic bronchitis will be evaluated.